OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2â¯months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9â¯months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7â¯months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).
Endoscopic angle-resolved light scattering methods have been developed for early cancer detection but they typically require multi-element coherent fiber optic bundles to recover scattering distributions from tissues. Recent work has focused on using a single multimode fiber (MMF) to measure angle resolved scattering but this approach has practical limitations to overcome before clinical translation. Here we address these limitations by proposing an MMF-based endoscope capable of measuring angular scattering patterns suitable for determining structure. Significantly, this approach implements a spectrally resolved detection scheme to reduce speckle and leverages the azimuthal symmetry of the angular scattering patterns to enable measurements that are robust to fiber bending. This results in a unique method that does not require matrix inversion or machine learning to measure a transmitted scattering distribution. The MMF utilized here is 1000 mm in length with a 200â µm core and is demonstrated to recover angular scattering distributions even with bending displacements of up to 30â cm. This advance has a significant impact on the clinical translation of biomedical endoscopic diagnostic techniques that use angular scattering to determine the size of cell nuclei to detect early cancer.
Prior research has established the psychometric properties of the Critical Warzone Experiences (CWE) scale among post-9/11 Iraq/Afghanistan-era veterans; however, the psychometric properties of the CWE among Gulf War I-era veterans have not yet been established. The first objective of the present study was to examine the psychometric properties of the CWE among Gulf War I-era veterans. The second objective was to test the hypothesis that the CWE would have a significant indirect effect on suicidal thoughts and behaviors via posttraumatic stress disorder (PTSD) and depressive symptoms. To test these hypotheses, a survey packet that included the CWE and measures of PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors was administered to 1,153 Gulf War I-era veterans. Consistent with prior research in post-9/11 Iraq/Afghanistan-era veterans, the CWE exhibited good internal consistency (α = .85), a unidimensional factor structure (RMSEA = .056, CFI = .959, SRMR = .033; average factor loading = .69), and good concurrent validity with PTSD (r = .47, p < .001) and depressive (r = .31, p < .001) symptoms among Gulf War I-era veterans. Additionally, as hypothesized, a significant indirect effect from the CWE to suicidal thoughts and behaviors via PTSD and depressive symptoms (ß = .35, p < .001) was also observed. Taken together, our findings provide strong support for using the CWE with Gulf War I-era veterans.
INTRODUCTION: Obstructive azoospermia occurs when there is a blockage in the male reproductive tract, leading to a complete absence of sperm in the ejaculate. It constitutes around 40% of all cases of azoospermia (1, 2). Blockages in the male reproductive tract can arise from either congenital or acquired factors, affecting various segments such as the epididymis, vas deferens, and ejaculatory ducts (3). Examples of congenital causes encompass conditions like congenital bilateral absence of the vas deferens and unexplained epididymal blockages (4). Acquired instances of obstructive azoospermia may result from factors like vasectomy, infections, trauma, or unintentional injuries caused by medical procedures (5). This complex condition affecting male fertility, presents two main treatment options: microsurgical reconstruction and surgical extraction of sperm followed by in vitro fertilization (IVF). Microsurgical reconstruction proves to be the most cost-effective option for treating obstructive azoospermia when compared with assisted reproductive techniques (6, 7). However, success rates of reconstruction defined by patency are as high as 99% for vasovasostomy (VV) but decline to around 65% if vasoepididymostomy (VE) is required (8, 9). Thus, continued refinement in technique is necessary in order to attempt to improve patency for patients undergoing VE. In this video, we show a comprehensive demonstration of microsurgical VE, highlighting the innovative epididymal occlusion stitch. The goal of this innovative surgical technique is to improve outcomes for VE. MATERIALS AND METHODS: The patient is a 39-year-old male diagnosed with obstructive azoospermia who presents for surgical reconstruction via VE. His partner is a 37-years-old female with regular menstrual cycles. The comprehensive clinical data encompasses a range of factors, including FSH levels, results from semen analysis, and outcomes from testicular sperm aspiration. This thorough exploration aims to provide a thorough understanding of our innovative surgical technique and its application in addressing complex cases of obstructive azoospermia. RESULTS: The procedure was started on the right, the vas deferens was identified and transected. The abdominal side of the vas was intubated and a vasogram performed, there was no obstruction. There was no fluid visible from the testicular side of the vas for analysis, thus we proceeded with VE. Upon inspection of the epididymis dilated tubules were identified. After selecting a tubule for VE, two 10-0 nylon sutures were placed, and it was incised. Upon inspection of the fluid motile sperm was identified. After VE, we performed a novel epididymal occlusion stitch technique. This was completed distal to the anastomosis by placing a 7-0 prolene through the tunica of the epididymis from the medial to lateral side. This stitch was then tightened down with the goal to largely occlude the epididymis so that sperm will preferentially travel through the anastomosis. The steps were then repeated on the left. At 3-month follow up, the patient had no change in testicular size as compared with preoperative size (18cc), he had no testicular or incisional discomfort, and on semen analysis he had presence of motile sperm. After 3 months post-surgery, the patient had motile sperm seen on semen analysis. DISCUSSION: The introduction of a novel epididymal occlusion stitch demonstrates a targeted strategy to enhance the success of microscopic VE. Encouragingly, a 3-month post-surgery follow-up reveals the presence of motile sperm, reinforcing the potential efficacy of our approach. This is promising given the historical lower patency, delayed time to patency, and higher delayed failure rates that patients who require VE experience (10). In total, 40% of all azoospermia cases can be attributed to obstruction. The conventional treatments for obstructive azoospermia involve microsurgical reconstruction and surgical sperm retrieval followed by IVF. While microsurgical reconstruction has proven to be economically viable, the quest for enhanced success rates has led to the exploration of innovative techniques. Historically, the evolution of VV and VE procedures, initially performed in the early 20th century, laid the foundation for contemporary microsurgical approaches (11). Notably, the microscopic VV demonstrated significant improvements in patency rates and natural pregnancy likelihood, as evidenced by the seminal Vasovastomy Study Group study in 1991 (8). In contemporary literature, success rates particularly for VE remain unchanged for the past three decades since the original published success rates by the Vasectomy Reversal Study Group (12). VE is associated with a longer time to patency as well with patients taking 2.8 to 6.6 months to have sperm return to ejaculate as compared to 1.7 to 4.3 months for those undergoing VV. Additionally, of those patients who successfully have sperm return to the ejaculate after VE up to 50% will have delayed failure compared to 12% for those undergoing VV who are patent. Finally, of those who experience delayed failure after undergoing VE it usually occurs earlier with studies reporting as early as 6 months post-operatively (10). Given the lack of improvement and significantly worsened outcomes with VE further surgical refinement is a constant goal for surgeons performing this procedure. CONCLUSION: In conclusion, this video is both a demonstration and a call to action for commitment to surgical innovation. We aim to raise the bar in VE success rates, ultimately bringing tangible benefits to patients and contributing to the ongoing evolution of reproductive medicine. The novel epididymal occlusion stitch emerges as a beacon of progress, promising not only enhanced safety but also potential reductions in patency time. Surgical excellence and methodological refinement, as exemplified in this video, lay the foundation for a future where male reproductive surgery continues to break new ground.
Azoospermia , Epididymis , Vas Deferens , Vasovasostomy , Male , Azoospermia/surgery , Epididymis/surgery , Humans , Vas Deferens/surgery , Vas Deferens/abnormalities , Vasovasostomy/methods , Treatment Outcome , Microsurgery/methods , Suture Techniques , Reproducibility of Results
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cancer with often poor outcomes. Limited biomarkers exist for predicting clinical outcomes. The Merkel cell polyomavirus (MCPyV) serum antibody test (AMERK) has shown potential for indicating better recurrence-free survival in a single-institution study. The study aimed to evaluate the link between initial AMERK serostatus and survival. Secondary objectives included examining the relationship between initial AMERK titer levels and tumor burden. METHODS: A retrospective cohort study across two institutions analyzed patients tested with AMERK within 90 days of MCC diagnosis. Regression models assessed the association of survival outcomes with serostatus, considering various factors. The relationship between AMERK titer and tumor burden indicators was evaluated using ANOVA. Significance testing was exploratory, without a fixed significance level. RESULTS: Of 261 MCC patients tested, 49.4% were initially seropositive (titer ≥75). Multivariable analysis showed that seropositivity improved recurrence, event-free, overall, and MCC-specific survival rates. Strong associations were found between initial AMERK titer and clinical, tumor, and nodal stages, tumor size, and disease extent. Notably, improved survival with seropositivity was observed only in patients with localized disease at initial presentation. CONCLUSION: Circulating antibodies to MCPyV oncoproteins, as indicated by the AMERK test, are linked with better survival in MCC patients with localized disease at presentation. This could enhance patient risk profiling and treatment personalization. The study's retrospective nature and exploratory analysis are key limitations. PLAIN LANGUAGE SUMMARY: Merkel cell carcinoma (MCC) is a potentially aggressive skin cancer, and tools to predict patient outcomes are limited. A blood test called anti-Merkel cell panel (AMERK), which checks for specific antibodies related to this cancer, might give us some clues. In this study, we looked at 261 MCC patients who took the AMERK test within 90 days of diagnosis. We found that patients with an initial positive AMERK result tended to have better outcomes, especially if their cancer was in the early stages. However, it is important to note that this study has limitations, including using retrospective data and exploratory analyses.
Objective: This study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. Methods: MDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). Results: Agreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. Conclusions: LSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.
Estimating distributions for cryptic and highly range-restricted species induces unique challenges for species distribution modeling. In particular, bioclimatic covariates that are typically used to model species ranges at regional and continental scales may not show strong variation at scales of 100s and 10s of meters. This limits both the likelihood and usefulness of correlated occurrence to data typically used in distribution models. Here, we present analyses of species distributions, at 100 × 100 m resolution, for a highly range restricted salamander species (Shenandoah salamander, Plethodon shenandoah) and a closely related congener (red-backed salamander, Plethodon cinereus). We combined data across multiple survey types, account for seasonal variation in availability of our target species, and control for repeated surveys at locations- all typical challenges in range-scale monitoring datasets. We fit distribution models using generalized additive models that account for spatial covariates as well as unexplained spatial variation and spatial uncertainty. Our model accommodates different survey protocols using offsets and incorporates temporal variation in detection and availability resulting from survey-specific variation in temperature and precipitation. Our spatial random effect was crucial in identifying small-scale differences in the occurrence of each species and provides cell-specific estimates of uncertainty in the density of salamanders across the range. Counts of both species were seen to increase in the 3 days following a precipitation event. However, P. cinereus were observed even in extremely wet conditions, while surface activity of P. shenandoah was associated with a more narrow range. Our results demonstrate how a flexible analytical approach improves estimates of both distribution and uncertainty, and identify key abiotic relationships, even at small spatial scales and when scales of empirical data are mismatched. While our approach is especially valuable for species with small ranges, controlling for spatial autocorrelation, estimating spatial uncertainty, and incorporating survey-specific information in estimates can improve the reliability of distribution models in general.
We present first results from a dark photon dark matter search in the mass range from 44 to 52 µeV (10.7-12.5 GHz) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area 0.5 m^{2} and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon photon mixing parameters χâ³10^{-12} in this range at 90% confidence level. This surpasses existing constraints by about 2 orders of magnitude and is the most stringent bound on dark photons in this range below 49 µeV.
PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.
Accounting for intraspecific and interspecific competition when assessing the effects of chemical and nonchemical stressors is an important uncertainty in ecological risk assessments. We developed novel projection of interspecific competition (PIC) matrices that allow for analysis of population dynamics of two or more species exposed to a given stressor(s) that compete for shared resources within a landscape. We demonstrate the application of PIC matrices to investigate the population dynamics of two hypothetical fish species that compete with one another and have differences in net reproductive rate and intrinsic rate of population increase. Population status predictions were made under scenarios that included exposure to a chemical stressor that reduced fecundity for one or both species. The results of our simulations demonstrated that measures obtained from the life table and Leslie matrix of an organism, including net reproductive rate and intrinsic rate of increase, can result in erroneous conclusions of population status and viability in the absence of a consideration of resource limitation and interspecific competition. This modeling approach can be used in conjunction with field monitoring efforts and/or laboratory testing to link effects due to stressors to possible outcomes within an ecosystem. In addition, PIC matrices could be combined with adverse outcome pathways to allow for ecosystem projection based on taxonomic conservation of molecular targets of chemicals to predict the likelihood of relative cross-species susceptibility. Overall, the present study shows how PIC matrices can integrate effects across the life cycles of multiple species, provide a linkage between endpoints observed in individual and population-level responses, and project outcomes at the community level for multiple generations for multiple species that compete for limited resources. Environ Toxicol Chem 2024;43:1406-1422. Published 2024. This article is a U.S. Government work and is in the public domain in the USA.
Fishes , Population Dynamics , Animals , Risk Assessment , Ecosystem , Models, Biological , Water Pollutants, Chemical/toxicity , Reproduction/drug effects
PURPOSE: To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS: Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS: Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION: Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Squamous Cell , Cisplatin , Deoxycytidine , Gemcitabine , Radiotherapy, Intensity-Modulated , Vulvar Neoplasms , Humans , Female , Middle Aged , Vulvar Neoplasms/pathology , Vulvar Neoplasms/radiotherapy , Vulvar Neoplasms/drug therapy , Vulvar Neoplasms/mortality , Vulvar Neoplasms/therapy , Radiotherapy, Intensity-Modulated/methods , Radiotherapy, Intensity-Modulated/adverse effects , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Adult , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Deoxycytidine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/methods , Progression-Free Survival
Hyperreflective foci (HRFs) appear in optical coherence tomography (OCT) images of the retina and vitreous of patients with various ocular diseases. HRFs are hypothesized to be immune cells that appear in response to ischemia or tissue damage. To accurately identify HRFs and establish their clinical significance, it is necessary to replicate the detection of similar patterns in vivo in a small animal model. We combined visible-light OCT with temporal speckle averaging (TSA) to visualize and track vitreal HRFs (VHRFs) densities for three days after an optic nerve crush (ONC) injury. Resulting vis-OCT images revealed that VHRF density significantly increased approximately 10-fold at 12â h after ONC and returned to baseline three days after ONC. Additional immunohistochemistry results confirmed these VHRFs as inflammatory cells induced from optic nerve damage.
Optic Nerve Injuries , Tomography, Optical Coherence , Humans , Mice , Animals , Tomography, Optical Coherence/methods , Retina/diagnostic imaging , Optic Nerve Injuries/diagnostic imaging , Optic Nerve/diagnostic imaging
The large COVID-19 outbreaks in prisons in the Washington (USA) State Department of Corrections (WADOC) system during 2020 highlighted the need for a new public health approach to prevent and control COVID-19 transmission in the system's 12 facilities. WADOC and the Washington State Department of Health (WADOH) responded by strengthening partnerships through dedicated corrections-focused public health staff, improving cross-agency outbreak response coordination, implementing and developing corrections-specific public health guidance, and establishing collaborative data systems. The preexisting partnerships and trust between WADOC and WADOH, strengthened during the COVID-19 response, laid the foundation for a collaborative response during late 2021 to the largest tuberculosis outbreak in Washington State in the past 20 years. We describe challenges of a multiagency collaboration during 2 outbreak responses, as well as approaches to address those challenges, and share lessons learned for future communicable disease outbreak responses in correctional settings.
COVID-19 , Tuberculosis , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Public Health , Prisons , Washington/epidemiology , Pandemics/prevention & control , Disease Outbreaks/prevention & control , Tuberculosis/epidemiology , Tuberculosis/prevention & control
Protein and sugar content are important seed quality traits in soybean because they improve the value and sustainability of soy food and feed products. Thus, identifying Quantitative Trait Loci (QTL) for soybean seed protein and sugar content can benefit plant breeders and the soybean market by accelerating the breeding process via marker-assisted selection. For this study, a population of recombinant inbred lines (RILs) was developed from a cross between R08-3221 (high protein and low sucrose) and R07-2000 (high sucrose and low protein). Phenotypic data for protein content were taken from the F2:4 and F2:5 generations. The DA7250 NIR analyzer and HPLC instruments were used to analyze total seed protein and sucrose content. Genotypic data were generated using analysis via the SoySNP6k chip. A total of four QTLs were identified in this study. Two QTLs for protein content were located on chromosomes 11 and 20, and two QTLs associated with sucrose content were located on chromosomes 14 and. 11, the latter of which co-localized with detected QTLs for protein, explaining 10% of the phenotypic variation for protein and sucrose content in soybean seed within the study population. Soybean breeding programs can use the results to improve soybean seed quality.
Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have demonstrated the contribution of this field to medicine. Properly designed and implemented platforms can drastically reduce drug development timelines and costs. While such efforts were initially focused primarily on target affinity/activity, it is now appreciated that other parameters are equally important in the successful development of a drug and its progression to the clinic, including pharmacokinetic properties as well as absorption, distribution, metabolic, excretion and toxicological (ADMET) properties. In the last decade, several programs have been developed that incorporate these properties into the drug design and optimization process and to varying degrees, allowing for multi-parameter optimization. Here, we introduce the Artificial Intelligence-driven Drug Design (AIDD) platform, which automates the drug design process by integrating high-throughput physiologically-based pharmacokinetic simulations (powered by GastroPlus) and ADMET predictions (powered by ADMET Predictor) with an advanced evolutionary algorithm that is quite different than current generative models. AIDD uses these and other estimates in iteratively performing multi-objective optimizations to produce novel molecules that are active and lead-like. Here we describe the AIDD workflow and details of the methodologies involved therein. We use a dataset of triazolopyrimidine inhibitors of the dihydroorotate dehydrogenase from Plasmodium falciparum to illustrate how AIDD generates novel sets of molecules.
Artificial Intelligence , Drug Design , Algorithms , Evolution, Molecular
There is an ethical need to document and develop best practices for meeting ambassador animals' welfare needs within the context of meeting zoo and aquarium program objectives. This is because ambassador animals experience direct and frequent contact with humans. This paper rigorously synthesizes behavioral research and theory, contemporary practices, and personal experiences to offer key concepts that can be applied to meet ambassador animal welfare needs. These key concepts include addressing an animal's recognition of choice and control, the use of the most positive and least intrusive effective interventions when training animals to participate in programming, and an overall reduction in aversive strategy use. Our model for increasing ambassador animal welfare focuses on seven main areas of concern, including the following: choosing the most suitable animal for the program; choosing the human with the right skills and knowledge for the program; using the most positive, least intrusive, effective training methods; developing a strong trusting relationship between trainer and animal; developing a comprehensive enrichment program; the need for institutional support; and creating opportunities for animals to practice species-appropriate behaviors. Our model will provide guidelines for improved ambassador animal welfare that can be refined with future research.
Background and purpose: Little is known about the applicability, utilization, and effectiveness of mind-body interventions (MBIs) for conditions that are not predominantly pain, neoplastic, or psychiatric, particularly in pediatric patients. This scoping review describes research pertaining to such interventions in youth with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Methods: Searches of EBSCO CINAHL, Elsevier Scopus, Ovid for MEDLINE, and Ovid PsycInfo were conducted to investigate MBIs in youth under 18 years of age with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Articles published between 2010 and 2020 were included. Abstracts were screened by three authors for inclusion, and disagreements were resolved by a designated author. Selected full-text articles were divided among all authors for review of study quality, intervention feasibility and acceptability, and effectiveness. Results: The search yielded 1010 titles with 15 meeting the final inclusion criteria, studying a total of 641 youth. Participants ranged in age from 6 to 19 years (included studies had data on participants <18 years reported separately); 61.5% were female (n = 394) and 38.5% were male (n = 247). The two most common conditions studied were asthma and irritable bowel syndrome, with yoga being the most popular intervention. Overall, MBIs showed promising preliminary evidence for improving symptoms and quality of life in youth with chronic medical conditions. Conclusion: MBIs have been successfully delivered and show promise in symptom palliation and quality of life improvement for youth with a variety of chronic medical conditions. More data from high-quality randomized controlled trials are needed to further characterize the effectiveness of specific modalities for specific conditions.
There is no current consensus on the follow up of kidney function in patients undergoing cardiopulmonary bypass (CPB). The main objectives of this pilot study is to collect preliminary data on kidney function decline encountered on the first postoperative visit of patients who have had CPB and to identify predictors of kidney function decline post hospital discharge. Design: Retrospective chart review. Adult patients undergoing open heart procedures utilizing CPB. Patient demographics, type of procedure, pre-, intra-, and postoperative clinical, hemodynamic echocardiographic, and laboratory data were abstracted from electronic medical records. Acute kidney disease (AKD), and chronic kidney disease (CKD) were diagnosed based on standardized criteria. Interval change in medications, hospital admissions, and exposure to contrast, from hospital discharge till first postoperative visit were collected. AKD, and CKD as defined by standardized criteria on first postoperative visit. 83 patients were available for analysis. AKD occurred in 27 (54%) of 50 patients and CKD developed in 12 (42%) out of 28 patients. Older age was associated with the development of both AKD and CKD. Reduction in right ventricular cardiac output at baseline was associated with AKD (OR: 0.5, 95% CI: 0.3, 0.79, P = 0.01). Prolongation of transmitral early diastolic filling wave deceleration time was associated with CKD (OR: 1.02, 95% CI: 1.01, 1.05, P = 0.03). In-hospital acute kidney injury (AKI) was a predictor of neither AKD nor CKD. AKD and CKD occur after CPB and may not be predicted by in-hospital AKI. Older age, right ventricular dysfunction and diastolic dysfunction are important disease predictors. An adequately powered longitudinal study is underway to study more sensitive predictors of delayed forms of kidney decline after CPB.
Acute Kidney Injury , Renal Insufficiency, Chronic , Adult , Humans , Pilot Projects , Retrospective Studies , Longitudinal Studies , Cardiopulmonary Bypass/adverse effects , Kidney , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Renal Insufficiency, Chronic/etiology , Risk Factors , Acute Disease
